EBV PATHOGENESIS IN HIV-ASSOCIATED HAIRY LEUKOPLAKIA

毛状白斑（HLP）是人类免疫缺陷病毒（HIV）感染者常见的机会性感染。HLP发生在舌侧，由eb病毒（EBV）引起。HLP是EBV感染唯一的病理表现，也是EBV感染上皮细胞唯一的非恶性病变。HLP提供了深入了解EBV持续存在的机制和特定EBV基因产物在hiv相关EBV发病机制中的作用。三种假设将被验证：1)舌上皮细胞是hiv感染者持续EBV感染的第二个储存库。2) HLP是由潜伏和产生EBV基因的独特共表达引起的。3)发现了新的分子机制调控EBV基因在HLP中的独特表达模式。在一项临床研究方案中，hiv感染的HLP志愿者将接受抗病毒治疗，以抑制EBV复制并诱导BV潜伏期。随后停止抗病毒治疗将允许EBV再激活。舌头和血液淋巴细胞组织将被收集在抗病毒治疗之前，期间和之后。分子研究将研究EBV潜伏期和再激活的分子生物学和流行病学。基因表达在EBV发病机制中的作用将被研究，包括EBV基因序列变异和基因重组在HLP中的功能后果。最后，我们将探讨HIV-EBV相互作用在HLP发病机制中的作用。本研究结果将阐明EBV在HLP发病中的分子机制，适用于其他EBV相关疾病，包括鼻咽癌和hiv相关淋巴瘤。

Hairy leukoplakia (HLP) is a common opportunistic infection in human immunodeficiency virus (HIV)-infected individuals. HLP occurs on the lateral tongue and is caused by the Epstein-Barr virus (EBV). HLP is remarkable as the only pathologic manifestation of productive EBV infection and as the only non-malignant lesion of epithelial cell EBV infection. HLP offers insight into the mechanisms of EBV persistence and the role of specific EBV gene products in HIV-associated EBV pathogenesis. Three hypotheses will be tested: 1) That tongue epithelial cells are a second reservoir of persistent EBV infection in HIV-infected individuals. 2) That HLP results from a unique co-expression of both latent and productive EBV genes. 3) That novel molecular mechanisms regulate the unique pattern of EBV gene expression seen in HLP. In a clinical study protocol, HIV-infected volunteers with HLP will be treated with antiviral therapy to inhibit EBV replication and induce BV latency. Subsequent withdrawal of antiviral therapy will permit EBV reactivation. Tongue and blood lymphocyte tissues will be collected before, during, and after antiviral therapy. Molecular studies will investigate the molecular biology and epidemiology of EBV latency and reactivation. The role of gene expression in EBV pathogenesis will be investigated, including the functional consequences of EBV gene sequence variation and genetic recombination in HLP. Finally, the role of HIV-EBV interaction in HLP pathogenesis will be investigated. The results of this study will elucidate molecular mechanisms of EBV pathogenesis in HLP applicable to other EBV-associated diseases, including nasopharyngeal carcinoma and HIV-associated lymphomas.